The challenge area to be addressed is: Enabling Technologies: 06-DA-102, Tool Development for the Neurosciences. This application will use PET radioligand imaging, which is the only modality currently available to investigate the neurochemistry of cocaine addiction in the human brain in vivo. The advantage of this methodology is that it allows the more direct translation of animal research to human research, and can be used to determine the best neurochemical targets for future pharmacotherapy. In addition, we have developed a method that allows us to model relapse in the laboratory. This model is based on animal models of cocaine abuse, which show that a "priming" dose of cocaine reinstates self- administration. Using a similar laboratory model in humans allows us to correlate neurochemistry with the vulnerability to the reinforcing effects of cocaine. Previous preclinical studies have shown that the striatal mGluR5 plays a role in modulating dopamine and glutamate-dependent signaling within the striatum, which plays a critical role in the reinforcing effects of cocaine. In addition, preclinical studies show that cocaine exposure is associated with upregulation of the mGluR5. Thus, the goals of this study are to use PET to image the mGluR5 receptor in cocaine abuse and to investigate the relationship between receptor binding and relapse. Recent studies in animals have focused on mGluR5 glutamate receptor subtype, which may be upregulated in cocaine abuse. Thus, the goal of this application is to use Positron Emisssion Tomography and the new radiotracer [11C]ABP688 to image the mGluR5 receptor in human cocaine abusers and healthy controls, and to investigate its potential role in relapse. PUBLIC HEALTH RELEVANCE: Recent studies in animals have focused on mGluR5 glutamate receptor subtype, which may be upregulated in cocaine abuse. Thus, the goal of this application is to use Positron Emisssion Tomography and the new radiotracer [11C]ABP688 to image the mGluR5 receptor in human cocaine abusers and healthy controls, and to investigate its potential role in relapse.